A Digital Intervention for Post-Stroke Depression and Executive Dysfunction

Phase 2

Recruiting

• Conditions: Executive Dysfunction; Depression; Stroke
• Interventions: Device: AKL-T01; Behavioral: Metacognitive Strategy Training

• Registration Number: NCT05507138
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

Individuals with stroke commonly experience both depression and cognitive difficulties. The goal of this study is to evaluate the efficacy of a treatment that combines a digital therapeutic (an iPad-based cognitive training program) with learning cognitive strategies. The hypotheses are that this treatment will improve cognitive skills, depression symptoms, daily function, and brain connectivity. In the short-term, the findings will inform the efficacy of the intervention and in the long-term, may support the use of the intervention to improve co-occurring cognitive and mood difficulties after stroke.

Detailed Description

Post-stroke depression with executive dysfunction (DED) is associated with persistent mood and cognitive disturbance, poor social functioning, and disability. Existing interventions have limited evidence of efficacy, side effects, and can be difficult for stroke patients to access. This study aims to evaluate a remote digital intervention for post-stroke DED that combines iPad-based cognitive training using a program called AKL-T01 with virtual coaching to improve executive dysfunction, depression, and daily function after stroke. The primary hypothesis is that individuals randomized to the intervention arm (AKL-T01 + coaching) will demonstrate greater improvement in their executive functioning and depression symptoms and daily function relative to the comparator arm. The secondary hypothesis is that individuals randomized to the intervention arm will demonstrate greater increase in the functional connectivity of the executive control network (ECN, assessed with an MRI scan) at the conclusion of treatment, relative to participants randomized to the comparator arm.

Study Timeline

• Study First Submitted: 2022-08-16
• Study First Submitted QC: 2022-08-16
• Study First Posted: 2022-08-18
• Study Start: 2023-03-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-21
• Last Update Posted: 2024-05-22
• Primary Completion: 2026-05-01
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• first-time stroke that occurred 6 months or more prior to study initiation
• executive dysfunction as defined by a score of less than 1 standard deviation below age-adjusted normative score on at least one test of executive function in the screening assessment
• diagnosis of Major Depressive Episode assessed by the Structured Clinical Interview for the DSM-5 (SCID).
• at least moderate depressive symptoms as defined by Montgomery Asberg Depression Rating Scale ≥ 18
• motor function sufficient to operate an iPad and use a pen, based on self-report and observation
• if treated with an antidepressant medication, must be on a stable dose for a minimum of 8 weeks at the time of study enrollment.
• able to adhere to all testing and study requirements and willingness to participate in the full study duration

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Exclusion Criteria

• receptive aphasia as determined by a score of 2 or 3 on the NIH Stroke Scale [NIHSS] item 9 ("Best Language")
• dysarthria that makes speech unintelligible (score of 2 on NIHSS item #10)
• severe visual impairment or hemispatial neglect (score of 3 on NIHSS item #3 or score of 2 on NIHSS item #11)
• patient already enrolled in ongoing concurrent cognitive rehabilitation (note that if a subject is already enrolled in psychotherapy, this will not be grounds for exclusion)
• non-fluency in English
• presence of or history of significant neurologic or neurodegenerative disorder other than stroke
• presence of dementia based on dependence in basic ADLs due to cognitive deficits
• history of psychosis or mania (evaluated using the SCID).
• active suicide ideation (assessed via the Columbia Suicide Severity Rating Scale)
• severe executive dysfunction (based on clinical judgment during screening evaluation) precluding use of the iPad
• severe depression-even in the absence of active suicidal ideation-based on the screening evaluation and clinical judgment of the PI, which warrants a higher level of care and/or immediate referral to psychiatric services.
• pregnancy
• any other clinical or medical reason in the PI's initial screening evaluation that suggests the study is not appropriate for the participant.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AKL-T01	AKL-T01	Participants in the intervention group will complete 25 minutes of AKL-T01 per day, 5 days/week, for 6 weeks. AKL-T01 trains rapid multitasking on an iPad in an immersive videogame-like environment. Participants complete go/no-go + navigation exercises by moving the iPad to navigate a character on a path while tapping when a certain stimulus is presented and ignoring other stimuli. Participants will also receive weekly 45-minute metacognitive strategy coaching sessions delivered by a clinician. Sessions use guided questions and worksheets (shared virtually) to help participants reflect on their experience with AKL-T01 and link it to daily functioning, generate strategies for daily activities, and explore any emotional responses that arise during gameplay.
Enhanced Metacognitive Strategy Training	Metacognitive Strategy Training	In the control group, participants will complete-at the same frequency and duration as the intervention group-iPad-based games designed to provide general cognitive stimulation (word searches, checkers, and "spot the differences" between two pictures). Concurrently with these cognitive stimulation games, participants will receive weekly metacognitive strategy coaching sessions akin to that described above.
AKL-T01	Metacognitive Strategy Training	Participants in the intervention group will complete 25 minutes of AKL-T01 per day, 5 days/week, for 6 weeks. AKL-T01 trains rapid multitasking on an iPad in an immersive videogame-like environment. Participants complete go/no-go + navigation exercises by moving the iPad to navigate a character on a path while tapping when a certain stimulus is presented and ignoring other stimuli. Participants will also receive weekly 45-minute metacognitive strategy coaching sessions delivered by a clinician. Sessions use guided questions and worksheets (shared virtually) to help participants reflect on their experience with AKL-T01 and link it to daily functioning, generate strategies for daily activities, and explore any emotional responses that arise during gameplay.

Primary Outcome Measures

Name	Time	Method
Change in executive function, as measured by the Oral Symbol Digit Modalities Test (SDMT)	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the SDMT, a performance-based measure of divided attention/working memory with scores ranging from 0-120, with higher scores indicating better performance.

Secondary Outcome Measures

Name	Time	Method
Change in executive function, as measured by the Frontal Systems Behavior Rating Scale (FrSBe)	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the FrSBE, a brief behavioral rating scale for the assessment of behavior disturbances associated with damage to the frontal-subcortical brain circuits. The FrSBe is a 46-item rating scale with three subscales: Apathy, Disinhibition, and Executive Dysfunction. Raw scores range from 46 to 230 overall, which are converted to age adjusted T scores for the Apathy, Disinhibition, and Executive Dysfunction subscales. T scores \< 50 reflect less symptoms of apathy, disinhibition, and executive dysfunction. T scores \> 50 reflect greater symptoms of apathy, disinhibition, and executive dysfunction.
Change in daily function, as measured by the Neuro Quality of Life (NeuroQOL) Cognitive Function Short Form	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the Neuro Quality of Life (NeuroQOL) Cognitive Function Short Form, a self-report questionnaire of a person's perceived difficulties in cognitive abilities or in their application of such abilities to everyday tasks. Scores range from 8-40 with lower scores representing greater cognitive difficulties.
Change in executive function, as measured by the NIH Toolbox Flanker test	Baseline and end of treatment (6 weeks)	Change in total score in the active intervention arm vs. the comparator arm on the NIH Toolbox Flanker test, a timed iPad-based test of executive function where participants have to respond to certain stimuli while ignoring distractors. Score ranges between 0-10, with a higher score indicating better performance.
Change in depression symptoms, as measured by the 9-item Patient Health Questionnaire (PHQ-9)	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the PHQ-9, a self-report questionnaire of depression symptom frequency. Scores range from 0-27, where higher scores are indicative of greater depression symptoms.
Change in connectivity in the executive control network, as assessed by resting state functional MRI (rs-fMRI).	Baseline and end of treatment (6 weeks)	Change in functional connectivity in the active intervention arm vs. the comparator arm assessed by an rs-fMRI scan.
Change in depression symptoms, as measured by the Montgomery Asberg Depression Rating Scale (MADRS)	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the MADRS, a clinician-rated assessment of depression symptom severity that consists of 10 items; each item is rated on a 0-6 scale, resulting in a maximum total score of 60 points, with higher scores indicative of greater depression symptom severity.
Change in daily function, as measured by the performance-based Weekly Calendar Planning Activity (WCPA)	Baseline and end of treatment (6 weeks)	Change in score in the active intervention arm vs. the comparator arm on the WCPA, a performance based assessment that involves following and organizing a list of appointments or errands into a weekly schedule. Scoring is from 0-17 points, with higher scores indicating better performance.

Trial Locations

Locations (1)

Weill Cornell Medical Center; 🇺🇸 New York, New York, United States